Safety and Immunogenicity of a Vaccine Dendritic Cell-based Pulsed With Autologous Heat-inactivated in HIV-1 Infected Patients - Full Text View

Purpose

single-center, national clinical trial, phase I, randomized (1: 1: 1: 1), prospective, placebo-controlled, partially masked, parallel group. Patients will be assigned to one of the following four arms: 3 immunizations of dendritic cells / 3 immunizations of dendritic cells with pegylated interferon + / 3 immunizations of placebo / 3 immunizations of placebo with pegylated interferon.

Condition	Intervention	Phase
HIV Infection	Biological: DCV3 Biological: DCV3 with PEG-INF Biological: Placebo Biological: Placebo with PEG-INF	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Participant, Investigator Primary Purpose: Treatment
Official Title:	Safety and Immunogenicity of a Vaccine Dendritic Cell-based Pulsed With Autologous Heat-inactivated HIV in HIV-1 Infected Patients. Prospective, Randomized, Partially Blinded Study

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Further study details as provided by Judit Pich Martínez, Fundació Clínic per la Recerca Biomèdica:

Primary Outcome Measures:

Number of Participants with adverse events of grade 3 or higher [ Time Frame: 28 weeks ]
- Local adverse events of grade 3 or higher (pain and skin reactions including induration)
- Systemic adverse events of grade 3 or higher (fever, chills, headache, nausea, vomiting, malaise and myalgia)
- Clinical or laboratory confirmed grade 3 or higher on physical examination or retests adverse events Any event attributable to the vaccine involving a discontinuation of vaccination regime.
Virological [ Time Frame: 12 weeks ]
Proportion of patients with undetectable viral load (<37 copies / mL) at 12 weeks

Secondary Outcome Measures:

Number of adverse events grade 1 and 2 within 14 days after each immunization (weeks 2, 4 and 6) [ Time Frame: 6 weeks ]
Changes in the specific immune response [ Time Frame: 28 weeks ]
Measured by ELISPOT visits in weeks 2, 4, 8, 12, 16 and 28 compared to baseline and screening for dendritic cell vaccine and pegylated interferon.
Changes in levels of viral reservoir. [ Time Frame: 28 weeks ]
Measure the proviral DNA visits in the weeks -44, -36, 4, 8, 12, 16 and 28 compared to baseline and screening.
Proportion of patients with changes in any value of the levels of inflammatory markers, microbial translocation and immune activation [ Time Frame: 28 weeks ]
In visits at weeks 4, 16 and 28 compared compared to baseline and screening
Proportion of patients with viral rebound [ Time Frame: 15 days ]
Two consecutive obtaining measurements of plasma viral load> 37 copies / mL separated by at least 15 days after discontinuation of antiretroviral therapy.
Proportion of patients with autoimmunity markers induced by the vaccine as measured by: antithyroid antibodies (antithyroglobulin, antithyroid peroxidase), antinuclear antibodies, antiphospholipid antibodies and rheumatoid factors. [ Time Frame: 16 weeks ]
Evaluation on autoimmunity with antithyroid antibodies (antithyroglobulin, antithyroid peroxidase), antinuclear antibodies, antiphospholipid antibodies and rheumatoid factor at screening, baseline and week 16.
Changes in the transcriptome of patients visits weeks 4, 16 and 28 compared to baseline (week -12) [ Time Frame: 28 weeks ]
Weeks 4, 16 and 28 compared to baseline
Evaluation of the specific immune response trought IFN-gamma production in vitro at screening and baseline [ Time Frame: week 0 ]
Proportion of patients with IFN-gamma production in vitro measured by ELISPOT at screening and baseline
Evaluation of the specific immune response thought dendritic cell maturation markers in vitro at screening and baseline [ Time Frame: week 0 ]
Proportion of patients with dendritic cell maturation markers in vitro measured by flow cytometry at screening and baseline
Evaluation of the specific immune response thought T-cell proliferation in vitro at screening and baseline [ Time Frame: week 0 ]
Proportion of patients with T-cell proliferation in vitro measured by CFSE (carboxyfluorescein succinimidyl ester) at screening and baseline


Estimated Enrollment:	32
Study Start Date:	May 2016
Estimated Study Completion Date:	June 2018
Estimated Primary Completion Date:	May 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: DCV3 Autologus differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus	Biological: DCV3 Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus. Patients will receive three immunizations of dendritic cells during weeks 0, 2 and 4
Experimental: DCV3 with PEG-INF Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus with PEG-INF	Biological: DCV3 with PEG-INF Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded pulsed with autologous inactivated HIV virus with PEG_INF Patients will receive three immunizations of dendritic cells during weeks 0, 2 and 4 and INF during weeks 4,5 and 6
Placebo Comparator: CD placebo Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded	Biological: Placebo Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded Patients will receive three immunizations saline + 1% albumin during weeks 0, 2 and 4
Placebo Comparator: CD placebo + PEG-INF Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded with PEG-INF	Biological: Placebo with PEG-INF Autologous differentiated adult dendritic cells from monocytes of peripheral blood non expanded with PEG_INF Patients will receive three immunizations saline + 1% albumin during weeks 0, 2 and 4 and INF during weeks 4,5 and 6.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patient > 18 years of age;
Voluntarily sign informed consent;
Men or women with a negative pregnancy test before inclusion in the study;
HIV infection tested (with positive antibodies to HIV-1 and a detectable viral load);
Patient must be on stable treatment with cART at least 1 year
The average of all measurements of CD4 during the year before starting cART should be equal or greater than 350 cells / mm3
The number of CD4 + at enrollment must be equal or greater than 450 cells / mm3;
Plasma HIV viral load undetectable at least 6 months before the inclusion in the study, at least two determinations (occasional blips above the undetectable level are allowed).

Exclusion Criteria:

Treatment with suboptimal regimen (less than 3 antiretroviral drugs) before starting cART;
History of C CDC events;
Interruption of cART during the inclusion in the study;
Pregnancy woman or becoming pregnant in the next months;
Active opportunistic infections, or any active infection or cancer within 30 days prior to the screening visit;
Therapy with immunomodulatory agents, including cytokines (eg IL-2) and gamma globulins or chemotherapy within 90 days prior to the screening visit;
Use of anticoagulant medication;
Use of any investigational drug within 90 days prior to study entry;
Virological failure prior to antiretroviral treatment and / or mutations that confer resistance to antiretroviral drugs;
Uncontrolled psychiatric disorder;
Platelet count <80,000 / mm3;
Values ??of hemoglobin <12g / dL;
Patients with active uncontrolled autoimmune diseases;
Using contraindicated drugs in accordance with the Summary of Product Specifications of pegylated interferon;
Childbearing, or potential childbearing not using highly effective contraception;
Any other problem that according to the investigator could interfere with the evaluation of the objectives.
Any contraindication for the use of interferon peg in accordance with the Summary of Product Characteristics.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02767193

Contacts


Contact: Felipe García Alcaide, Doctor	+34 93 2275586	fgarcia@clinic.cat

Locations


Spain
Hospital Clínic	Recruiting
Barcelona, España, Spain, 08036
Contact: Felipe García, MD + 34 93 2275586 fgarcia@clinic.cat
Principal Investigator: Felipe García, MD

Sponsors and Collaborators

Judit Pich Martínez

More Information


Responsible Party:	Judit Pich Martínez, Clinical Research Manager, Fundació Clínic per la Recerca Biomèdica
ClinicalTrials.gov Identifier:	NCT02767193 History of Changes
Other Study ID Numbers:	DCV3/RisVac04 2015-001795-22 ( EudraCT Number )
Study First Received:	April 22, 2016
Last Updated:	April 5, 2017

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases	Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases

ClinicalTrials.gov processed this record on July 17, 2017